Synthesis, Crystal Structure and Biological Activity of Two Triketone-Containing Quinoxalines as HPPD Inhibitors

Abstract

Two new triketone-containing quinoxaline derivatives were designed by fragment splicing strategy and synthesized using 3,4-diaminobenzoic acid and substituted cyclohexanedione as starting materials. Both compounds were characterized by IR, 1H and 13C NMR, HRMS and X-ray diffraction. 3-Hydroxy-5-methyl-2-(quinoxaline-6-carbonyl)cyclohex-2-en-1-one (6a) crystallized in the triclinic system, space group Pī, a = 7.9829(2) Å, b = 8.1462(2) Å, c = 10.7057(3) Å, α = 84.3590(10)°, β = 89.7760(10)°, γ = 87.4190(10)°, Z = 2, V = 692.12(3) Å3, F(000) = 296, Dc = 1.335 Mg/m3, m(MoKa) = 0.095 mm–1, R = 0.0683 and wR= 0.1983. 3-Hydroxy-5,5-dimethyl-2-(3-ethoxyquinoxaline-6-carbonyl)cyclohex-2-en-1-one (6b) crystallized in the monoclinic system, space group P21/c, a = 10.1554(6) Å, b = 9.6491(6) Å, c = 17.7645(10) Å, β = 90.784(2)°, Z = 4, V = 1740.59(18) Å3, F(000) = 720, Dc = 1.299 Mg/m3, m(MoKa) = 0.092 mm–1, R = 0.0462 and wR = 0.1235. Physicochemical property comparison and ADMET prediction showed that compound 6a had similar properties to the commercial herbicide mesotrione. Molecular docking results showed that the interactions between 6a and AtHPPD were similar to mesotrione. Moreover, the extended aromatic ring system and the additional alkyl form more interactions with the surrounding residues. Examination of AtHPPD inhibition and herbicidal activity showed that 6a had similar inhibition values to mesotrione and had a superior inhibitory effect on Echinochloa crus-galli.

Keywords

• triketone-containing quinoxaline derivatives
• synthesis
• single-crystal structure
• molecular structure information
• herbicidal activity